Fucosterol Protects against Concanavalin A-Induced Acute Liver Injury: Focus on P38 MAPK/NF-κB Pathway Activity.

Wenhui Mo,Yujing Xia,Sainan Li,Wenwen Wang,Jingjing Li,Xiya Lu,Chuanyong Guo,Kan Chen,Ling Xu,Chengfen Wang

doi:10.1155/2018/2824139

Abstract

Objective Fucosterol is derived from the brown alga Eisenia bicyclis and has various biological activities, including antioxidant, anticancer, and antidiabetic properties. The aim of this study was to investigate the protective effects of fucosterol pretreatment on Concanavalin A- (ConA-) induced acute liver injury in mice, and to understand its molecular mechanisms. Materials and Methods Acute liver injury was induced in BALB/c mice by ConA (25 mg/kg), and fucosterol (dissolved in 2% DMSO) was orally administered daily at doses of 25, 50, and 100 mg/kg. The levels of hepatic necrosis, apoptosis, and autophagy associated with inflammatory cytokines were measured at 2, 8, and 24 h. Results Fucosterol attenuated serum liver enzyme levels and hepatic necrosis and apoptosis induced by TNF-α, IL-6, and IL-1β. Fucosterol also inhibited apoptosis and autophagy by upregulating Bcl-2, which decreased levels of functional Bax and Beclin-1. Furthermore, reduced P38 MAPK and NF-κB signaling were accompanied by PPARγ activation. Conclusion This study showed that fucosterol could alleviate acute liver injury induced by ConA by inhibiting P38 MAPK/PPARγ/NF-κB signaling. These findings highlight that fucosterol is a promising potential therapeutic agent for acute liver injury.

Highlights

The liver is the largest organ within the abdominal cavity and undertakes important physiological processes
These results showed that liver cells in the Concanavalin A (ConA) group demonstrated nuclear condensation and fragmentation, and the cell outline disappeared and was replaced by an amorphous, red-colored granular coagulation or liquefied substance
We evaluated TNF-α, IL-6, and IL-1β, the major mediators in Concanavalin A- (ConA-)induced liver injury, and found that their expression was consistent with the extent of necrosis, apoptosis, and autophagy

Summary

Introduction

The liver is the largest organ within the abdominal cavity and undertakes important physiological processes. Liver injury is the basis of acute liver failure and is primarily caused by viral infections, drugs, food additives, alcohol, and radioactive damage [1]. It is important to establish an animal model to screen effective drugs. ConA can modify the major histocompatibility complex (MHC) structure to produce inflammatory reactions, by activating macrophages and CD4+ T cells, which release TNF-α, IL-1β, IL-6, and other inflammatory factors that damage hepatic cells [4]. The model has the advantages of utilizing a simple extraction and causing liver-specific damage (injury to other organs is not obvious), providing a reliable animal model for clinical research in basic immunology [5]. Peroxisome proliferatoractivated receptors (PPARs) are ligand-activated transcription factors that regulate lipid metabolism, blood pressure, cell growth, and differentiation [6,7,8]. PPARs are divided into three subtypes, PPARα, PPARβ, and PPARγ, which all regulate

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Discussion

Conclusion